Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that affects at least 1.5 million Americans. Current immunosuppressive treatments are effective but can be accompanied by infections and toxicity, especially when applied over a longer period of time. Hence, there remains a significant unmet need for safe and more effective treatments. It is well established that patients with SLE are marked by reduced regulatory T cells and acquired deficiency of interleukin-2 (IL-2). Transient treatment with low-dose recombinant IL-2 increases regulatory T cell number while blocking T follicular helper cells. Hence, the treatment reduced autoantibody formation and immune complex deposition without inducing systemic immune suppression. These data strongly support development of IL-2 based therapy. Importantly, low-dose rIL-2 therapy safely achieved significant efficacy in a small clinical trial. However, current low-dose rIL-2 therapy has a very short half-life and causes local reaction at injection sites, with an unwanted increase in several innate immune cell types such as natural killer cells and eosinophils. To obtain ideal outcomes in patients, we have designed a long-acting IL-2 analog, APT602, that promises to generate low and stable circulating levels of IL-2 related agonist. The innovative drug candidate will enable selective stimulation of regulatory T cells while minimizing negative clinical effects. Importantly, a better efficacy and safety profile has been demonstrated in multiple animal models. The specific aim of this Phase I SBIR proposal is to determine whether twice weekly treatment with mAPT602 for 8 weeks will more effectively halt the disease progression for 100 days of follow-up, compared with low-dose rmIL-2 (recombinant murine IL2) in the mouse model of SLE at the time of disease onset.